Linked Life Data

9302281

Source:http://linkedlifedata.com/resource/pubmed/id/9302281

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1998-1-2
pubmed:abstractText
Tuberous sclerosis is an autosomal dominant trait in which the dysregulation of cellular proliferation and differentiation results in the development of hamartomatous growths in many organs. The TSC2 gene is one of two genes determining tuberous sclerosis. Inactivating germline mutations of TSC2 in patients with tuberous sclerosis and somatic loss of heterozygosity at the TSC2 locus in the associated hamartomas indicate that TSC2 functions as a tumour suppressor gene and that loss of function is critical to expression of the tuberous sclerosis phenotype. The TSC2 product, tuberin, has a region of homology with the GTPase activating protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in vitro. Here we show that the region of homology between tuberin and human rap1GAP and the murine GAP mSpa1 is more extensive than previously reported and spans approximately 160 amino acid residues encoded within exons 34-38 of the TSC2 gene. Single strand conformation polymorphism analysis of these exons in 173 unrelated patients with tuberous sclerosis and direct sequencing of variant conformers together with study of additional family members enabled characterisation of disease associated mutations in 14 cases. Missense mutations, which occurred in exons 36, 37 and 38 were identified in eight cases, four of whom shared the same recurrent change P1675L. Each of the five different missense mutations identified was shown to occur de novo in at least one sporadic case of tuberous sclerosis. The high proportion of missense mutations detected in the region of the TSC2 gene encoding the GAP-related domain supports its key role in the regulation of cellular growth.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1991-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9302281-Amino Acid Sequence, pubmed-meshheading:9302281-Animals, pubmed-meshheading:9302281-Female, pubmed-meshheading:9302281-GTP-Binding Proteins, pubmed-meshheading:9302281-GTPase-Activating Proteins, pubmed-meshheading:9302281-Humans, pubmed-meshheading:9302281-Male, pubmed-meshheading:9302281-Mice, pubmed-meshheading:9302281-Molecular Sequence Data, pubmed-meshheading:9302281-Mutation, pubmed-meshheading:9302281-Pedigree, pubmed-meshheading:9302281-Phenotype, pubmed-meshheading:9302281-Proteins, pubmed-meshheading:9302281-Rats, pubmed-meshheading:9302281-Repressor Proteins, pubmed-meshheading:9302281-Sequence Homology, Amino Acid, pubmed-meshheading:9302281-Tuberous Sclerosis, pubmed-meshheading:9302281-Tumor Suppressor Proteins, pubmed-meshheading:9302281-rap GTP-Binding Proteins, pubmed-meshheading:9302281-ras GTPase-Activating Proteins
pubmed:year
1997
pubmed:articleTitle
The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis.
pubmed:affiliation
Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't